Bairagi et al.

Burns & Trauma (2019) 7:33

https://doi.org/10.1186/s41038-019-0165-0

STUDY PROTOCOL Open Access

Comparative effectiveness of Biobrane®,

RECELL® Autologous skin Cell suspension
and Silver dressings in partial thickness
paediatric burns: BRACS randomised trial
protocol
Anjana Bairagi1,2,3* , Bronwyn Griffin1,2,3, Zephanie Tyack1,4,6, Dimitrios Vagenas5, Steven M. McPhail4,7 and
Roy Kimble1,2,3,6

Abstract
Background: Mixed partial thickness burns are the most common depth of burn injury managed at a large
Australian paediatric hospital specialty burns unit. Prolonged time until re-epithelialisation is associated with
increased burn depth and scar formation. Whilst current wound management approaches have benefits such as
anti-microbial cover, these are not without inherent limitations including multiple dressing changes. The Biobrane®
RECELL® Autologous skin Cell suspension and Silver dressings (BRACS) trial aims to identify the most effective
wound management approach for mixed partial thickness injuries in children.
Methods: All children presenting with an acute burn injury to the study site will be screened for eligibility. This is a
single-centre, three-arm, parallel group, randomised trial. Children younger than 16 years, with burns ≥ 5% total
body surface area involving any anatomical location, up to 48 h after the burn injury, and of a superficial partial to
mid-dermal depth, will be included. A sample size of 84 participants will be randomised to standard silver dressing
or a Regenerative Epithelial Suspension (RES™) with Biobrane® or Biobrane® alone. The first dressing will be applied
under general anaesthesia and subsequent dressings will be changed every 3 to 5 days until the wound is ≥ 95%
re-epithelialised, with re-epithelialisation time the primary outcome. Secondary outcomes of acute pain, acute itch,
scar severity, health-related quality of life, treatment satisfaction, dressing application ease and healthcare resource
use will be assessed at each dressing change and 3, 6 and 12 months post-burn injury.
Discussion: The findings of this study can potentially change the wound management approach for superficial
partial to mid-dermal burns in children locally and worldwide.
Trial registration: The Australian New Zealand Clinical Trials Registry (ACTRN12618000245291) approved
prospective registration on 15 February 2018. Registration details can be viewed at https://www.anzctr.org.au/Trial/
Registration/TrialReview.aspx?id=374272&isReview=true.
Keywords: Partial thickness burns, Children, Regenerative epidermal suspension, Re-epithelialisation, Wound healing

* Correspondence: anjana.bairagi@hdr.qut.edu.au
1
Centre for Children’s Burns and Trauma Research, Centre for Children’s
Health Research, Brisbane, Queensland, Australia
2
Pegg Leditschke Children’s Burns Centre, Queensland Children’s Hospital,
Brisbane, Queensland, Australia
Full list of author information is available at the end of the article

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Bairagi et al. Burns & Trauma (2019) 7:33
Background
Burns are the fifth most common cause of non-fatal injur-
ies in children younger than 16 years [1]. Paediatric burn
injuries are associated with the burden of both functional
and psychological challenges to the child [2–4] as well as
the considerable expense incurred to health service pro-
viders who manage the burn care [5]. In 2017, three-
fourths of acute burns treated at the Queensland Chil-
dren’s Hospital in Brisbane and approximately half of re-
corded burn cases across Australia and New Zealand [6]
were partial thickness burn injuries. The available wound
management options are not without inherent disadvan-
tages including but not limited to delayed wound healing
[7–12]. Thus, current practice is driven to facilitate faster
wound re-epithelialisation to improve scar outcomes [13]
and reduce healthcare costs [10, 14].
Partial thickness burn injuries have a varied time to re-
epithelialisation. Superficial partial thickness burns ideally
heal within 14 days without requiring surgical interven-
tion. Typically, deep partial thickness wounds are antici-
pated to have a prolonged time to re-epithelialisation
(TTRE), often requiring a skin graft. Mid-dermal thickness
wounds can potentially re-epithelialise spontaneously,
within 14 days and without surgical intervention [15].
However, this is not always the status quo and manage-
ment of intermediate depth burns remains contentious.
Some surgeons prefer early skin grafting, whereas others
advocate for conservative non-surgical management.
One third of paediatric burns will develop hyper-
trophic scar, if wound re-epithelialisation occurs be-
tween 14 and 21 days [15–17]. It is presumed that
children have an increased collagen production rate
hence the higher incidence of hypertrophic scar forma-
tion as compared with adults [18]. In a systematic re-
view, Vloemans et al. found that membranous dressings
were better than topical standard of care options for the
treatment of partial thickness scald burns in children
[19]. However, there was no clear recommendation re-
garding the best membranous dressing for treatment of
partial thickness paediatric burns [16]. Burn depth,
TTRE and hypertrophic scar have an established associ-
ation [13, 15–17]. Yet, despite advances in wound man-
agement approaches, the ideal dressing to manage
partial thickness burns in children remains undefined.
The three wound management approaches to be investi-
gated in this trial are a topical anti-microbial dressing,
epidermal replacement using an autologous skin cell
suspension and dermal salvage using a biosynthetic skin
substitute.
Topical silver impregnated dressings used as the stand-
ard of care at the study site are (i) Acticoat® (Smith and
Nephew, Hull, UK) with Mepitel® (Mölnlycke, Göteborg,
Sweden) or (ii) Mepilex Ag® (Mölnlycke, Göteborg,
Sweden) alone [9]. Acticoat®, is a multi-layered
Page 2 of 12
polyethylene nanocrystalline silver pad that is attached to
a soaking coat of polyester [20] and has been in clinical
use since 1993. When compared to silver sulphadiazine
ointment, Acticoat® is safe, cost-effective and reduces the
TTRE, requirement for grafting and long term scar man-
agement in paediatric burn injuries [21–23] . Mepitel® is a
silicone-coated, nylon dressing with a silicone wound
interface layer. Acticoat® combined with Mepitel deliver
antimicrobial properties of silver nanocrystalline particles
and an atraumatic pain-free wound contact layer. This
promotes faster re-epithelialisation by minimising wound-
related trauma and pain [24].
Mepilex Ag® is a silver sulfate soft silicone foam dressing
that allows for continuous silver delivery to the wound, good
exudate management, provides a moist environment and
thermal insulation making this dressing ideal for partial
thickness burns [25]. In a randomised trial of children (n =
96) with partial thickness burns, silver-impregnated foam
dressings were effective in shortening the TTRE and re-
duced pain during dressing changes [9]. Despite this, silver
impregnated dressings are more expensive per dressing
change when compared to Biobrane® and a Regenerative
Epithelial Suspension (RES™) [10], require frequent dressing
changes due to non-transparent design and are associate
with adverse effects such as cytotoxicity and argyria. Over
the last 30 years, epithelial suspension preparation for burn
wound management has undergone a multitude of transfor-
mations including the number of enzymatic degradation
agents used, co-delivery systems with various cell carriers
and a range of preparation times (few weeks to under an
hour) [7, 26]. The RECELL® Autologous Cell Harvesting
(ACH) device (Avita Medical, California, USA) was first in-
troduced almost two decades ago [27]. In approximately 30
min, a Regenerative Epithelial Suspension (RES™) containing
basal keratinocytes, melanocytes, fibroblasts, melanocytes,
Langerhans cells and epidermal basal cells [28] is obtained
from a donor skin sample as small as 1 cm2. The faster
preparation allows for a readily available suspension com-
pared to the cultured keratinocytes, where wait times can be
a few weeks.
Few studies have comprehensively assessed the effect-
iveness of the RES™ in the management of childhood
burn injuries. Most of the published literature is based
on the adult cohort and there is a paucity of data based
on the paediatric population. When compared to stand-
ard care, wounds treated with RES™ had longer operative
times [29], more wound infection [10] and once applied
the RES™ requires a retention dressing such as Biobrane®,
to keep in situ [10]. However, in the other studies, appli-
cation of RES™ was associated with less post-operative
pain [10, 29], smaller donor site area [29, 30], shorter
TTRE [10, 29, 30], fewer dressing changes and cost-ef-
fectiveness [10, 31]. Autologous skin cell suspensions
show promising potential to change current burn wound
Bairagi et al. Burns & Trauma (2019) 7:33
management approaches from dressing based to cell-
based therapy.
First introduced in 1979 [11], Biobrane® (Smith and
Nephew, Hull, UK) is a composite biosynthetic skin sub-
stitute composed a matrix of short porcine collagen pep-
tides bonded to a layer of nylon that is enveloped in
silicone [8]. The benefits of using Biobrane® include
shorter TTRE, improved mobility, shorter hospital stay,
ease of application, ability to visualise the wound [32]
and reduced pain [10–12, 33, 34]. For clean wounds, this
transparent dressing is able to stay in situ for up to 14
days, thus supporting the cost-effective treatment of
burn injuries [35]. Failure of Biobrane® to adhere to the
wound bed occurs once counts exceed 105 organisms/
gram of tissue [36]. Reported infection rates associated
with Biobrane® range from 5 to 22% [12, 37, 38]. How-
ever, Lal. et al. demonstrated that infection rate upon
application of Biobrane® to superficial partial thickness
scald burns in children with 48 h of injury did not differ
when compared to a topical silver dressing [39]. Bio-
brane® recreates the barrier function of the skin and has
been used as a dermal salvage option for burn wounds
over the last four decades.
Aims
The Biobrane®, RECELL® Autologous skin Cell suspen-
sion and Silver dressings Trial (BRACS Trial), will evalu-
ate partial thickness, paediatric and burn injuries with
the following aims:
Primary
To evaluate the effectiveness of three wound manage-
ment approaches (standard care silver dressings (Acti-
coat® and Mepitel® or Mepilex Ag®)) or an autologous
skin cell suspension (ASCS, harvested with the RECELL®
ACH device) with Biobrane® or Biobrane® alone, in redu-
cing the re-epithelialisation time of superficial partial to
mid-dermal thickness burn injuries in children.
Secondary
To examine the effectiveness of three wound manage-
ment approaches in the same group of children for redu-
cing pain, itch, scar severity and healthcare resource use
as well as, improving health-related quality of life, treat-
ment satisfaction and dressing application ease.
Study design
The BRACS Trial is a parallel group, single-centre and
randomised trial. The null hypothesis is that there is no
difference between the three intervention groups. The
alternative hypothesis is that there is a statistically sig-
nificant difference between the interventions. If null hy-
pothesis is not rejected, this is still important, as treating
clinicians will be able to select an intervention knowing
Page 3 of 12
that patient well-being will not be compromised. An ac-
tive treatment control group (group A: standard silver
dressings) was included as it was considered unethical to
use a placebo group for this study.
Methods
Study setting
This single-centre study will be conducted at a major
paediatric burn centre in Brisbane, Queensland,
Australia. This large state hospital has a catchment area
spanning more than 1.73 million km2 and with a popula-
tion of approximately 5 million inhabitants [40]. The
centre treats over 1200 new burns patients annually.
Eligibility criteria
All new patients attending the study site will be evalu-
ated for eligibility. Children younger than 16 years, who
have sustained a burn of superficial partial thickness to
mid-dermal depth, within 48 h of injury and with a total
body surface area burned (TBSAB) ≥ 5% as assessed by
the attending burns surgeon, will be included. To allow
for patients who travel from regional referring centres to
be included, application of silver-impregnated dressings
onto wounds prior transfer to the study setting will be
included. Patients with superficial burns, deep dermal to
full thickness depth wounds and injuries deemed not
compatible with life by the attending burns surgeon, will
be excluded from participation in the study, see Fig. 1.
Recruitment
Treating clinicians of all children presenting to the study
setting will determine eligibility for enrolment in the
study based on the set inclusion and exclusion criteria.
Participant (where applicable) ‘assent’ is sought at the re-
cruitment of each potential participant. Once guardian
permission is confirmed, informed consent for participa-
tion will be obtained by an investigator aligned with the
study. A translator will be present for all participants of
non-English speaking background throughout the study.
All participants and their guardians will be given an op-
portunity to discuss the study with the investigator prior
to signed consent. Participants, who decline enrolment
into the study, will be assigned standard care and only
their de-identified data will be collected.
Interventions
Eligible participants will be randomised to one of the
three interventions:
Group A: standard silver dressings. Silver dressings will
be applied ((i) Acticoat® with Mepitel® or (ii) Mepilex
Ag®) as per standard protocol at the study site.
Group B: Biobrane® combined with RES™
Group C: Biobrane® only.
Bairagi et al. Burns & Trauma (2019) 7:33
Fig. 1 Biobrane®, RECELL® Autologous skin Cell suspension and Silver dressings (BRACS) Trial flow diagram. SPT superficial partial thickness, MD
mid-dermal, TBSAB total body surface area burned, RES™ Regenerative Epithelial Suspension, HRU Healthcare Resource Use, HRQOL Health-related
quality of life, OPD outpatient department
Operative procedures
The initial dressing application will be completed under
a general anaesthesia for all consented participants
under aseptic conditions. The operative timeline is illus-
trated in Table 1. For eligibility to enrol, the attending
burns surgeon will determine TBSAB and this will be
the primary approach for TBSAB assessment. The in-
accuracy of human TBSAB assessment arises from vari-
ability associated with children, body mass index and
gender [41]. Consequently, the secondary measure to es-
timate TBSAB will be the NSW Trauma Application
and E-Burn Application. Available software programs
have found some application but not much validation
[42–44] and stems from the idea of rapid accurate
TBSAB calculation to guide subsequent management.
These mobile applications facilitate instant TBSAB cal-
culation and both are used at the study centre and
worldwide.
Objective burn depth will be measured with the Moor
LDLS-BI Laser Doppler Imager® (Moor Instruments
Ltd., Axminster, and Devon, UK). The reported sensitiv-
ity and specificity of Laser Doppler Imaging (LDI) in
predicting outcome of paediatric injuries when com-
pared with clinician assessment ranges from 80.6–97%
and 76.9–100% [45–47], respectively. The assessment of
Page 4 of 12
burn depth by the attending burns surgeon will be taken
as the primary approach. Burn depth assessed with LDI
will be the secondary approach and measured at the ini-
tial dressing application after randomisation. Burn depth
assessment using LDI in the first 48 h post-burn injury
has been showed to be accurate [48–51] and is used to
record burn depth progression and not guide clinical
practice at the study site.
A three-part process will be required for the initial
dressing application of participants in group B that
includes harvesting of donor skin, preparation and appli-
cation of the ASCS to the wound followed by Biobrane®
and secondary dressings. A suitable donor site, where
possible, will be identified adjacent to the wound. The
size of skin sample will be based on the TBSAB as deter-
mined by the RES™ preparation guidelines. A donor sam-
ple of healthy skin will be obtained at a depth of 0.15
mm (0.006 in.) in depth using a pneumatic dermatome
(Zimmer, Dover, Ohio, USA). The correct thickness of
donor is evidenced by an almost translucent sample that
leaves behind pinpoint bleeding at the donor site, the
edges of the sample do not curl and there is an absence
of the white dermis surface. Any excess RES™ if present
will be applied to the donor site then dressed with Cuti-
cerin® (Smith and Nephew Medical Ltd., Hull, UK). The
Bairagi et al. Burns & Trauma (2019) 7:33
Table 1 Initial dressing application procedure
RESTM Regenerative Epidermal Suspension, ACH Autologous cell farvesting, FR French gauge
sequence of secondary dressings used in groups B and C
will maintain moisture, allow for absorption of exudate
and a degree of compression to minimise disturbance of
the fragile epidermal surface. Application of these dress-
ing changes is not required under general anaesthesia
unless otherwise indicated. The attending burns surgeon
or paediatric surgery registrar assigned to the care of the
patient will apply the RES™ and Biobrane®. Both doctors
and nurses will apply the standard silver dressings.
Page 5 of 12
Post-operative care
Post-operatively, all in-patient participants will receive
multi-disciplinary support as part of rehabilitation in-
cluding allied health, multi-modal analgesia, and critical
care for those hospitalised in the intensive care unit.
Participants deemed fit to be discharged from the hos-
pital in between the dressing changes prior to full re-
epithelialisation; will be given a standardised patient in-
formation card with emergency numbers and basic
Bairagi et al. Burns & Trauma (2019) 7:33 Page 6 of 12

Table 2 Data collection and assessment timeline for the trial

COD change of dressing, DOI date of injury, TBSAB total body surface area burned, 3D three-dimensional, 2D two-dimensional, FLACC Face, Legs, Activity, Cry,
Consolability, FPS-R Faces Pain Scale-Revised, NRS-P Numeric Rating Scale–Pain, NRS-P Proxy Numeric Rating Scale–Pain Proxy, NRS-I Numeric Rating Scale–Itch,
NRS-I Proxy Numeric Rating Scale–Itch Proxy, POSAS Patient and Observer Scar Assessment Scale, BBSIP Brisbane Burn Scar Impact Profile, CHU9D Child Health
Utility 9D, RES™ Regenerative Epithelial Suspension
Bairagi et al. Burns & Trauma (2019) 7:33
dressing advice. In addition, participants will be advised
to report any concerns regarding the dressing to staff at
the study setting especially should fever or erythema de-
velop at home. A schematic representation of the assess-
ment timeline is illustrated in Table 2.
Monitoring
Minimal adverse events are expected from the proposed
interventions. At the study centre, known potential ad-
verse events (e.g. infection, haematoma, intensive care
admissions) have a standardised management protocol.
Adverse events related to the interventions will be moni-
tored through review of patient medical records, by
guardian and participant (where applicable) self-report
and by the treating clinicians. All adverse events will be
communicated to the clinical health service and Human
Research Ethics Committee (HREC). Discontinuation or
alteration of treatment will be at the discretion of the
treating clinical team. An independent Safety Monitor-
ing Group will also monitor all aspects of patient safety
throughout the study on a regular basis. An interim ana-
lysis will be completed by an independent statistician,
who will be blinded to the treatment allocation after a
minimum of 30 participants have been recruited.
Study outcomes
Primary outcome: TTRE
Wound re-epithelialisation time is defined as the num-
ber of days from date of burn injury to ≥ 95% wound re-
epithelialisation or date of skin graft as determined by
the attending burns surgeon. Subjective assessment by
an experienced burn surgeon is validated and reliable
and will be the primary approach for TTRE [52, 53]. Ob-
jective assessment with three-dimensional (3D) digital
camera imaging will be the secondary approach. Wound
re-epithelialisaton will be expressed as a percentage
using wound area (cm2) and perimeter (cm) calculated
on the first dressing change day and the day a clinical as-
sessment of ≥ 95% wound re-epithelialisation is made by
the attending burns surgeon. The first dressing change is
usually within 3 to 5 days after the burn injury. This al-
lows for the burn wound to declare full extent and rep-
resent the maximal possible wound area in the absence
of infection.
Images taken with the 3D LifeVizII System® (Quantifi-
care S.A., Cedex, France) will be analysed using Derma-
pix® v3.0 (Quantificare S.A., Cedex, France). This fast,
non-invasive 3D clinical imaging approach is ideal for
children. The 3D LifeVizII System®/Dermapix® has been
validated in the assessment of partial thickness burn in-
juries (intraclass correlation coefficient (ICC) 0.96, 95%
confidence intervals (CI) 0.93–0.97) [54, 55]. However,
the Dermapix® software is time-consuming as it requires
the images to be first uploaded, then stitched and lastly,
Page 7 of 12
analysed. Hence, using Dermapix® does not provide a
real-time analysis of the wound.
A second 3D camera, the Intel® RealSense™ Depth
Camera D415 (Intel, CA, USA) with corresponding GPC
3D WoundCare (GPC, Swansea, UK) software will be
used as a second secondary objective measure of TTRE.
The reliability of the WoundCare Lite (ICC 0.985, 95%
CI 0.905–0.996) [41] and instantaneous availability of
analysed data output is advantageous over the 3D LifeVi-
zII System®/Dermapix®. Validation in the paediatric burn
wound population is currently in progress, as this tech-
nology is relatively new.
Secondary outcome
Assessment of secondary outcomes will begin from
initial dressing application and continue until the 12-
month follow-up review as illustrated in Fig. 1 and
Table 2.
Acute pain
An 11-point numeric rating scale-pain (NRS-P) scores
pain from 0 (no pain) to 10 (worst possible pain) [56,
57]. A proxy report of pain (NRS-P Proxy) by guardians
of all participants will be the primary approach for acute
pain. The Face, Legs, Activity, Cry and Consolability
(FLACC) scale is an observational pain measure that has
been validated for peri-procedural pain in children [58,
59] and scores pain intensity by rating five behaviours
on a 3-point scale (0 to 2): face, legs, activity, consolabil-
ity and cry. The revised Faces Pain Scale-Revised (FPS-
R) utilises a horizontal scale of six facial expressions with
assigned numeric values from 0 to 10 (0, 2, 4, 6, 8, 10),
with 10 denoting maximal pain intensity [60]. Acute
peri-procedural pain will be assessed subjectively by self-
report from participants aged ≥ 8 years who are compe-
tent at seriation testing using the NRS-P and FPS-R pain
scales. Behavioural observations will be made by both
clinicians (FLACC scale) and guardian of all participants
(NRS-P Proxy).
All sedation and analgesia administered at the dressing
change will be documented. Pain assessments will be
completed before and after dressing removal and appli-
cation. This will be adhered to as much as is practically
possible. In some circumstances, such as whilst under
general anaesthesia, it will not be able to document par-
ticipant self-report nor behavioural observations. Peri-
procedural distraction techniques including bubbles,
food, mobile device and toy that are part of standard
care will also be recorded.
Itch
Acute post-burn pruritis will be measured with an 11-
point itch NRS-I (0 = no pruritis to 10 = worst imagin-
able pruritis) until the wound is ≥ 95% re-epithelialised.
Bairagi et al. Burns & Trauma (2019) 7:33
Participants ≥ 8 years will self-report (NRS-I). A proxy
report of participant itch (NRS-I proxy) will be taken
from the accompanying guardian for all participants and
will the primary approach for itch. The NRS-I has shown
good correlation when compared with visual analogue
scale and Itch Man Scale and is easier to use in the
evaluation of itch intensity [61, 62]. The itch item of the
Patient and Observer Scar Assessment Scale (POSAS)
will be used to assess chronic pruritis and will be evalu-
ated by all participants 8 years or older as well as by all
guardians (POSAS Patient) and by an investigator
(POSAS Observer) [63].
Scar severity
The re-epithelialised wound will be evaluated for the se-
verity of scars using objective (ultrasonography and col-
orimetry) and subjective (POSAS and Brisbane Burn
Scar Impact Profile (BBSIP)) measures [63–66]. The ob-
jective measures are the principal approach based on
evidence of the ability to detect change. Scar thickness
will be measured using the portable Venue40 MSK®
Ultrasound machine (GE Healthcare, Fairfield, CT,
USA). Ultrasound test-retest and interrater reproduci-
bility of scar thickness is acceptable for paediatric
scars [67].
Scar colorimetry will be evaluated with the DSM II Col-
orMeter® (Cortex Technology, Hadsund, Denmark). This
device uses tristimulus reflectance, colorimetry and nar-
row-band photometry to assess scar lightness (L*), ery-
thema (a*) and pigmentation (b*) [68]. An average of three
measurements of L*, a*, b* from both the scar and healthy
skin will be recorded. The primary measure of scar pig-
mentation and scar erythema will be L* and a* respectively.
Both the investigator and guardian of all participants
will complete the POSAS. This survey assesses scar
thickness, vascularity, pliability, pigmentation and relief,
as well as patient scale items of itch, pain, colour, stiff-
ness, thickness and irregularity [63]. The BBSIP physical
scar subscales and BBSIP sensory subscale will also
measure scar severity [64–66]. An investigator having
completed scar assessment training to the satisfaction of
the occupational therapist at the study site will complete
the scar assessments of all participants.
Health-related quality of life (HRQOL)
The BBSIP measures HRQOL and patient-reported scar
characteristics for individuals with burn scars [64–66].
The Child Health Utility 9D (CHU9D) is a preference-
based measure that assesses both participant HQROL
and resource utilisation of the interventions [69–72].
Participant guardians will complete both HRQOL assess-
ments for all participants.
Page 8 of 12
Treatment satisfaction
Treatment satisfaction is a patient-reported outcome
[73] that guides quality of service delivery by a treating
health service provider. In a study of parents (n = 62) of
children receiving burn treatment, the perceived support
and respectful communication by clinicians was strongly
associated with the quality of received care [74]. Both
clinicians and participant guardian will complete an 11-
point NRS (0 = not at all satisfied to 10 = extremely satis-
fied) to measure treatment satisfaction.
Ease of dressing application
The ease of dressing application will be assessed using a
questionnaire regarding the dressings (application ease,
dressing conformability, dressing application duration)
including additional space for comments by treating
clinicians.
Healthcare resource use
Healthcare resource use related to the management of
burn injuries will be collected for each patient from the
perspective of the healthcare provider with a 12-month
time-horizon. Healthcare resource use to be collected
for each participant will include trial interventions and
other wound management-related resource use. In
addition, product(s) used in wound and scar manage-
ment as well as associated clinician labour time (e.g. for
assessments and treatments during outpatient clinic ap-
pointments). Resource use for burn-related hospitalisa-
tions (e.g. intensive care admission) will also be
collected. Resource use will be costed at market rates
(e.g. industrial award rates for clinician labour time,
standing offer arrangement rates for products supplied,
values consistent with the (Australian) Independent
Hospital Pricing Authority for hospitalisation costs).
Data management
Sample size estimate
The sample size estimate conducted for this trial is
based on the primary outcome of TTRE. Using the
Power Analysis and Sample Size (PASS) software (ver-
sion 11.0.7; PASS, NCSS, LLC), a two-sided logrank test
procedure was used. A total sample size of 84 subjects
(28 participants per group) that accounted for a 10% at-
trition rate would achieve 80% power at a significance
level of 0.05 [10, 75, 76]. A clinically important differ-
ence of 4 days for re-epithelialisation was used for the
sample size estimation.
Randomisation and allocation
To reduce the chance of prediction of treatment alloca-
tion, a procedure which randomly allocates participants
in groups using a random step size will be used [77].
The randomisation sequence will then be uploaded into
Bairagi et al. Burns & Trauma (2019) 7:33
Research Electronic Data Capture (REDCap) randomisa-
tion module [78] by a third party person not associated
with the study. Upon obtaining informed consent for the
participation, baseline data (participant demographics
including Fitzpatrick Skin Type, burn injury time, depth,
TBSAB, injury mechanism and history of first aid prior
to enrollment) will be collected. An investigator aligned
with the study will complete the randomisation using
REDCap and inform the treating clinicians of the allo-
cated intervention group.
Blinding
Once data collection is complete, a panel of burn wound
specialists inclusive of preselected burn surgeons and
nurses will conduct a blinded review of wound and scar
imaging. Any possible identifying material that could in-
dicate to the blinded assessors, which group the partici-
pant, was allocated to, will be removed from images.
The participants and their care providers will be blinded
to their intervention assignment. Although it will be un-
avoidable to detect remnants of silver dressing in some
cases, it is anticipated that it will be almost impossible to
differentiate between the group B and group C. An expe-
rienced radiographer from the study centre will
complete blinded assessments of scar thickness.
Statistical analysis
In the exploratory stage, data will be graphed, and
summary statistics will be calculated for all outcomes.
Data will be analysed using the ‘Intention to Treat’
principle. The primary outcome data will use the sur-
vival analysis model (both Kaplan-Meier analysis and
Cox proportional hazards regression), with the time to
healing as the main outcome and dressing group as the
explanatory variable. All other data will be analysed
using appropriate methods for longitudinal data such as
mixed model’s regression analysis or generalised estimat-
ing equations (GEE). A GEE is better suited for estimat-
ing population average effects whereas mixed models are
better suited for understanding the source of correlation
and its structure. Thus, they are complementary ways of
analysing the data rather than opposing. It should also
be noted that for symmetrical outcome variable distribu-
tions (such as normally distributed) both methods
should give similar results. Statistical significance will be
set at p < 0.05. The data set will be analysed with SPSS
(IBM Corporation, Armonk, NY, USA) and Stata
(StataCorp, College Station, TX, USA) software where
appropriate.
Data collection and storage
Data collection will be in the form of completion of
questionnaires and clinical imaging (2D and 3D
photographs, laser Doppler imaging and sonography),
Page 9 of 12
colorimetry, assessments of pain, itch intensity, treat-
ment satisfaction, ease of dressing application,
HRQOL, wound intervention fidelity, healthcare re-
source utilisation and scar severity as well as partici-
pant demographics, socioeconomic status and clinical
characteristics. Data collection and management will
be completed by an investigator and entered into the
REDCap software [78] system for managing the data.
At the study site, the de-identified data will be kept
in a locked filing cabinet and backed up onto the
Queensland University of Technology (QUT), Re-
search Data Storage Service. This data will be stored
for 15 years after the completion of the trial in ac-
cordance with National Health and Medical Research
Council guidelines. Results of this study are to be
published in peer-reviewed journals and presented at
national and international burns conferences. This
protocol was completed in accordance with the
SPIRIT 2013 guidelines [79, 80].
Discussion
The overall reported rate of hypertrophic scar formation
in children ranges from 17 to > 50% in children [17]. To
avoid the costly burden of managing burn scars and the
impact on participants and families, current wound
management approaches focus on shortening re-epithe-
lialisation time. An ideal skin substitute provides effect-
ive and scar free healing. However, current wound
management approaches incorporate some but not all
properties of a functioning integumentary system thus
the debate continues regarding how best to treat these
burn wounds. For children with larger TBSAB, faster
TTRE assists these burn survivors to begin the process
of rehabilitation earlier, enables earlier return to routine
daily activities and reduces scarring.
Effective pain management is of paramount import-
ance, from both a psychological and clinical perspective
in paediatric burn patients. Sub-optimal peri-procedural
analgesia was significantly associated with a 2.2% delay
in re-epithelialisation, for every point increase in pain
measured using the FPS-R [81]. In addition, reducing
the number of dressing changes may reduce the poten-
tial pain and distress associated with dressing changes.
Post-burn pruritis causes much distress in children and
has a moderate association with mental health [82]. Un-
controlled scratching hinders the re-epithelialisation
process and potentially disrupts the fragile newly regen-
erated epithelium. In addition, the potential introduction
of infective pathogens would also delay TTRE. Inevit-
ably, a proportion of children post mixed partial thick-
ness burn will develop a scar. A multi-disciplinary
approach that incorporates both operative (contracture
release, medical needling) and non-operative treatments
Bairagi et al. Burns & Trauma (2019) 7:33
(topical silicone, pressure garments) is vital to successful
scar management. Efficient health resource utilisation
improves the quality of health care provided to current
and future children with mixed partial thickness burn
injuries and most importantly enables clinicians to make
informed decisions on best practice.
Based on past trials and studies at the study site, a
limitation of this study is the anticipated large dropout
rate. Potential attrition bias will be addressed by examin-
ing whether the extent and reasons for dropout are bal-
anced across the groups [83]. Although different
dropout rates across the three groups are not antici-
pated, a sensitivity analysis will be run to check for any
differences. It is expected that random drop out will re-
sult in larger confidence intervals but not bias. In
addition, if there is no imbalance, then attrition bias is
not likely to be a problem [83]. Limitations associated
with burn depth assessment and wound infection diag-
nosis will be adjusted for during statistical analysis. The
BRACS randomised trial will add new knowledge re-
garding the comparative effectiveness of autologous skin
cell suspension for the management of partial thickness
and paediatric burn injuries.
Trial status
Recruitment started in May 2018 and will proceed for a
period of 18 months. Follow-up consultations will be in
the outpatient setting at the 3, 6 and 12-month post-date
of burn injury. Intended completion of the study is De-
cember 2020.
Abbreviations
2D: Two-dimensional; 3D: Three-dimensional; ACH: Autologous cell
harvesting; ASCS: Autologous skin cell suspension; BBSIP: Brisbane Burn Scar
Impact Profile; BRACS: Biobrane®, RECELL® Autologous skin Cell suspension
and Silver dressings; CHU9D: Child Health Utility 9D; COD: Change of
dressing; DOI: Date of injury; FLACC: Face, Legs, Activity, Cry, Consolability;
FPS-R: Faces Pain Scale-Revised; GEE: Generalised Estimating Equations;
HREC: Human Research Ethics Committee; HRQOL: Health-related quality of
life; ICC: Intraclass correlation coefficient; LDI: Laser Doppler Imaging; NRS-I
Proxy: Numeric Rating Scale–Itch Proxy; NRS-I: Numeric Rating Scale–Itch;
NRS-P Proxy: Numeric Rating Scale–Pain Proxy; NRS-P: Numeric Rating Scale–
Pain; OPD: Outpatient department; POSAS: Patient and Observer Scar
Assessment Scale; QLD: Queensland; QUT: Queensland University of
Technology; REDCap: Research electronic data capture; RES™: Regenerative
Epithelial Suspension; SPIRIT: Standard Protocol Items Recommendations for
Interventional Trials; SSA: Site-specific approval; TBSAB: Total body surface
area burned; TTRE: Time to re-epithelialisation
Acknowledgements
The investigators would like to thank the participants and their families as
well as the staff of the study site for their continued support throughout the
trial.
Authors’ contributions
All authors contributed towards the study design. AB drafted the manuscript.
Critical review and editing of the final manuscript draft were done by all
authors. The final version of this manuscript was read and approved by all
the authors.
Page 10 of 12
Funding
Avita Medical has made available an industry research grant to be
administrated by QUT. However, Avita Medical will not have any input into
protocol design nor the conduct of the trial. The principal investigator is a
PhD candidate of QUT and has no financial interest in the products used in
this study. SMM is supported by an Australian National Health and Medical
Research Council administered fellowship(#1161138).
Availability of data and materials
Not applicable
Ethics approval and consent to participate
Ethics was obtained from the study site (HREC/17/QRCH/278, SSA/18/QRCH/
41 QUT HREC 80227). The trial is prospectively registered with the Australian
New Zealand Clinical Trials Registry (ACTRN12618000245291). Consent for
participation will be obtained from all eligible participants. Protocol
amendments will be communicated with both the study centre HREC and
the Australian New Zealand Clinical Trials Registry.
Consent for publication
Not applicable
Competing interests
A co-investigator of the study is a paediatric burns surgeon (RK) treating par-
ticipants at the study site; however, this surgeon will not have any role in
the participant recruitment or allocation to groups. All other authors declare
that they have no competing interests.
Author details
1
Centre for Children’s Burns and Trauma Research, Centre for Children’s
Health Research, Brisbane, Queensland, Australia. 2Pegg Leditschke Children’s
Burns Centre, Queensland Children’s Hospital, Brisbane, Queensland,
Australia. 3School of Nursing, Institute of Health and Biomedical Innovation,
Queensland University of Technology, Brisbane, Queensland, Australia.
4
Australian Centre for Health Services Innovation, Institute of Health and
Biomedical Innovation, School of Public Health and Social Work, Queensland
University of Technology, Brisbane, Queensland, Australia. 5Research Methods
Group, Institute of Health and Biomedical Innovation, Queensland University
of Technology, Brisbane, Queensland, Australia. 6The University of
Queensland, Brisbane, Queensland, Australia. 7Centre for Functioning and
Health Research, Metro South Hospital and Health Service, Brisbane,
Queensland, Australia.
Received: 2 December 2018 Accepted: 26 July 2019
References
1. Peck MD. Epidemiology and prevention of burns throughout the world.
Jeschke MG, Kamolz L-P, Sjöberg F, Wolf SE, editors. Vienna: Springer
Vienna; 2012.
2. Simons M, Price N, Kimble R, Tyack Z. Patient experiences of burn scars in
adults and children and development of a health-related quality of life
conceptual model: a qualitative study. Burns. 2016;42(3):620–32.
3. De Young AC, Kenardy JA, Cobham VE, Kimble R. Prevalence, comorbidity
and course of trauma reactions in young burn-injured children. J Child
Psychol Psychiatry. 2012;53(1):56–63.
4. Maskell J, Newcombe P, Martin G, Kimble R. Psychosocial functioning
differences in pediatric burn survivors compared with healthy norms. J Burn
Care Res. 2013;34(4):465–76.
5. Hop MJ, Polinder S, Vlies CH, Middelkoop E, Baar ME. Costs of burn care: a
systematic review. Wound Repair Regen. 2014;22:436.
6. Tracy L, McInnes J, Gong J, Gabbe B, Thomas T. BRANZ 8th Annual Report_
Jul 16 - Jun 17. Burns registry of Australia and New Zealand; 2017.
7. Ter Horst B, Chouhan G, Moiemen NS, Grover LM. Advances in keratinocyte
delivery in burn wound care. Adv Drug Deliv Rev. 2018;123:18–32.
8. Watt SM, Pleat JM. Stem cells, niches and scaffolds: applications to burns
and wound care. Adv Drug Deliv Rev. 2018;123:82–106.
9. Gee Kee EL, Kimble RM, Cuttle L, Khan A, Stockton KA. Randomized
controlled trial of three burns dressings for partial thickness burns in
children. Burns. 2015;41(5):946–55.
Bairagi et al. Burns & Trauma (2019) 7:33
10. Wood F, Martin L, Lewis D, Rawlins J, McWilliams T, Burrows S, et al. A
prospective randomised clinical pilot study to compare the effectiveness of
Biobrane(R) synthetic wound dressing, with or without autologous cell
suspension, to the local standard treatment regimen in paediatric scald
injuries. Burns. 2012;38(6):830–9.
11. Mandal A. Paediatric partial-thickness scald burns–is Biobrane the best
treatment available? Int Wound J. 2007;4(1):15–9.
12. Lesher AP, Curry RH, Evans J, Smith VA, Fitzgerald MT, Cina RA, et al.
Effectiveness of Biobrane for treatment of partial-thickness burns in children.
J Pediatr Surg. 2011;46(9):1759–63.
13. Lonie S, Baker P, Teixeira RP. Healing time and incidence of hypertrophic
scarring in paediatric scalds. Burns. 2017;43(3):509–13.
14. Gee Kee E, Stockton K, Kimble RM, Cuttle L, McPhail SM. Cost-effectiveness
of silver dressings for paediatric partial thickness burns: an economic
evaluation from a randomized controlled trial. Burns. 2017;43(4):724–32.
15. Deitch EA, Wheelahan TM, Rose MP, Clothier J, Cotter J. Hypertrophic burn
scars: analysis of variables. J Trauma. 1983;23(10):895–8.
16. Cubison TC, Pape SA, Parkhouse N. Evidence for the link between healing
time and the development of hypertrophic scars (HTS) in paediatric burns
due to scald injury. Burns. 2006;32(8):992–9.
17. Chipp E, Charles L, Thomas C, Whiting K, Moiemen N, Wilson Y. A
prospective study of time to healing and hypertrophic scarring in paediatric
burns: every day counts. Burns Trauma. 2017;5(1):3.
18. Ketchum LD. Hypertrophic scars and keloids. Clin Plast Surg. 1977;4(2):301–10.
19. Vloemans AF, Hermans MH, van der Wal MB, Liebregts J, Middelkoop E.
Optimal treatment of partial thickness burns in children: a systematic
review. Burns. 2014;40(2):177–90.
20. Liu HF, Zhang F, Lineaweaver WC. History and advancement of burn
treatments. Ann Plast Surg. 2017;78(2 Suppl 1):S2–8.
21. Cuttle L, Naidu S, Mill J, Hoskins W, Das K, Kimble RM. A retrospective
cohort study of Acticoat versus Silvazine in a paediatric population. Burns.
2007;33(6):701–7.
22. Khundkar R, Malic C, Burge T. Use of Acticoat dressings in burns: what is the
evidence? Burns. 2010;36(6):751–8.
23. Hajska M, Dragunova J, Koller J. Cytotoxicity testing of burn wound
dressings: first results. Cell Tissue Bank. 2017;18(2):143–51.
24. White R, Morris C. Mepitel: a non-adherent wound dressing with Safetac
technology. Br J Nurs. 2009;18(1):58–64.
25. Silverstein P, Heimbach D, Meites H, Latenser B, Mozingo D, Mullins F, et al.
An open, parallel, randomized, comparative, multicenter study to evaluate
the cost-effectiveness, performance, tolerance, and safety of a silver-
containing soft silicone foam dressing (intervention) vs silver sulfadiazine
cream. J Burn Care Res. 2011;32(6):617–26.
26. Zhao H, Chen Y, Zhang C, Fu X. Autologous epidermal cell suspension: a
promising treatment for chronic wounds. J Tissue Viability. 2016;25(1):50–6.
27. Wood F. Clinical potential of autologous epithelial suspension. Wounds.
2003;15(1):16–22.
28. Fan C, Pek CH, Por YC, Lim GJS. Biobrane dressing for paediatric burns in
Singapore: a retrospective review. Singap Med J. 2018;59(7):360–5.
29. Gravante G, Di Fede MC, Araco A, Grimaldi M, De Angelis B, Arpino A, et al.
A randomized trial comparing ReCell system of epidermal cells delivery
versus classic skin grafts for the treatment of deep partial thickness burns.
Burns. 2007;33(8):966–72.
30. Holmes Iv JH, Molnar JA, Carter JE, Hwang J, Cairns BA, King BT, et al. A
comparative study of the ReCell(R) device and autologous spit-thickness
meshed skin graft in the treatment of acute burn injuries. J Burn Care Res.
2018;39(5):694–702.
31. Dunne JA, Rawlins JM. Early paediatric scald surgery—a cost effective dermal
preserving surgical protocol for all childhood scalds. Burns. 2014;40(4):777–8.
32. Austin RE, Merchant N, Shahrokhi S, Jeschke MG. A comparison of Biobrane
and cadaveric allograft for temporizing the acute burn wound: cost and
procedural time. Burns. 2015;41(4):749–53.
33. Greenwood JE, Clausen J, Kavanagh S. Experience with biobrane: uses and
caveats for success. Eplasty. 2009;9:e25.
34. Hyland EJ, D'Cruz R, Menon S, Harvey JG, La Hei E, Lawrence T, et al.
Biobrane (TM) versus acticoat (TM) for the treatment of mid-dermal
pediatric burns: a prospective randomized controlled pilot study. Int J Burns
Trauma. 2018;8(3):63–7.
35. Haddad AG, Giatsidis G, Orgill DP, Halvorson EG. Skin substitutes and
bioscaffolds: temporary and permanent coverage. Clin Plast Surg. 2017;
44(3):627–34.
Page 11 of 12
36. Woodruff E. Biobrane, a Biosynthetic Skin Prosthesis in Burn Wound
Coverings. DL W, editor. Boca Raton: CRC Press; 1984. p. c1984.
37. Demling RH. Use of Biobrane in the management of scalds. J Burn Care
Rehabil. 1995;16:329–30.
38. Phillips LG, Robson MC, Smith DJ, Phillips WA, Gracia WD, McHugh TP, et al.
Uses and abuses of a biosynthetic dressing for partial skin thickness burns.
Burns. 1989;15(4):254–6.
39. Lal S, Barrow RE, Wolf SE, Chinkes DL, Hart DW, Heggers JP, et al. Biobrane®
improves wound healing in burned children without increased risk of
infection. Shock. 2000;14(3):314–9.
40. Government Q. Queensland population counter: The State of Queensland
(Queensland Treasury) 2018. Available from: http://www.qgso.qld.gov.au/
products/reports/pop-growth-qld/qld-pop-counter.php.
41. Farrar E, Pujji O, Jeffery S. Three-dimensional wound mapping software
compared to expert opinion in determining wound area. Burns. 2017;
43(8):1736–41.
42. Fontaine M, Ravat F, Latarjet J. The e-burn application - a simple mobile
tool to assess TBSA of burn wounds. Burns. 2018;44(1):237–8.
43. Management NIoTaI. NSW Trauma App Analysis Report 21st August - 8th
November 2015. Institute of Trauma and Injury Management; 2015 27/01/2016.
44. Management NIoTaI. NSW Trauma App Analysis Report August 2015 – August
2016. NSW Institute of Trauma and Injury Management; 2016 22/02/2017.
45. Holland AJA, Martin HCO, Cass DT. Laser Doppler imaging prediction of
burn wound outcome in children. Burns. 2002;28(1):11–7.
46. La Hei ER, Holland AJ, Martin HC. Laser Doppler imaging of paediatric burns:
burn wound outcome can be predicted independent of clinical
examination. Burns. 2006;32(5):550–3.
47. Cho JK, Moon DJ, Kim SG, Lee HG, Chung SP, Yoon CJ. Relationship
between healing time and mean perfusion units of laser Doppler imaging
(LDI) in pediatric burns. Burns. 2009;35(6):818–23.
48. Mileski WJ, Atiles L, Purdue G, Kagan R, Saffle JR, Herndon DN, et al. Serial
measurements increase the accuracy of laser Doppler assessment of burn
wounds. J Burn Care Rehabil. 2003;24(4):187.
49. Jeng JC, Bridgeman A, Shivnan L, Thornton PM, Alam H, Clarke TJ, et al. Laser
Doppler imaging determines need for excision and grafting in advance of
clinical judgment: a prospective blinded trial. Burns. 2003;29(7):665–70.
50. Mill J, Cuttle L, Harkin DG, Kravchuk O, Kimble RM. Laser Doppler imaging in
a paediatric burns population. Burns. 2009;35(6):824–31.
51. Wang XQ, Mill J, Kravchuk O, Kimble RM. Ultrasound assessed thickness of
burn scars in association with laser Doppler imaging determined depth of
burns in paediatric patients. Burns. 2010;36(8):1254–62.
52. Bloemen M, Boekema B, Vlig M, van Zuijlen P, Middelkoop E. Digital image
analysis versus clinical assessment of wound epithelialization: a validation
study. Burns. 2012;38(4):501–5.
53. Bloemen MC, van Zuijlen PP, Middelkoop E. Reliability of subjective wound
assessment. Burns. 2011;37(4):566–71.
54. Stockton KA, McMillan CM, Storey KJ, David MC, Kimble RM. 3D
photography is as accurate as digital planimetry tracing in determining
burn wound area. Burns. 2015;41(1):80–4.
55. Gee Kee EL, Kimble RM, Stockton KA. 3D photography is a reliable burn
wound area assessment tool compared to digital planimetry in very young
children. Burns. 2015;41(6):1286–90.
56. Page MG, Katz J, Stinson J, Isaac L, Martin-Pichora AL, Campbell F. Validation
of the numerical rating scale for pain intensity and unpleasantness in
pediatric acute postoperative pain: sensitivity to change over time. J Pain.
2012;13(4):359–69.
57. von Baeyer CL, Spagrud LJ, McCormick JC, Choo E, Neville K, Connelly MA.
Three new datasets supporting use of the numerical rating scale (NRS-11)
for children’s self-reports of pain intensity. Pain. 2009;143:223.
58. Merkel S, Voepel-Lewis T, Shayevitz J, Malviya S. FLACC Pain Assessment
Tool: Reliability and Validation with Existing Tools. Anesthesiology. 1994;
81(SUPPLEMENT):A1360.
59. von Baeyer CL, Spagrud LJ. Systematic review of observational (behavioral)
measures of pain for children and adolescents aged 3 to 18 years. Pain.
2007;127(1–2):140–50.
60. Huguet A, Stinson JN, McGrath PJ. Measurement of self-reported pain
intensity in children and adolescents. J Psychosom Res. 2010;68(4):329–36.
61. Reich A, Halupczok J, Ramus M, Stander S, Szepietowski J. New Data on the
Validation of Vas and Nrs in Pruritus Assessment: Minimal Clinically
Important Difference and Itch Frequency Measurement. Acta Derm
Venereol. 2011;91(5):636.
Bairagi et al. Burns & Trauma (2019) 7:33 Page 12 of 12

62. Nieuwendijk SMP, de Korte IJ, Pursad MM, van Dijk M, Rode H. Post burn
pruritus in pediatric burn patients. Burns. 2018;44(5):1151–8.
63. Draaijers LJ. The patient and observer scar assessment scale: a reliable and
feasible tool for scar evaluation. Plast Reconstr Surg. 2003;113:1960.
64. Tyack Z, Kimble R, McPhail S, Plaza A, Simons M. Psychometric properties of
the Brisbane burn scar impact profile in adults with burn scars. PLoS One.
2017;12(9):e0184452.
65. Tyack Z, Ziviani J, Kimble R, Plaza A, Jones A, Cuttle L, et al. Measuring the
impact of burn scarring on health-related quality of life: development and
preliminary content validation of the Brisbane burn scar impact profile
(BBSIP) for children and adults. Burns. 2015;41(7):1405–19.
66. Simons M, Kimble R, McPhail S, Tyack Z. The longitudinal validity,
reproducibility and responsiveness of the Brisbane burn scar impact profile
(caregiver report for young children version) for measuring health-related
quality of life in children with burn scars. Burns. 2019. Article in Press.
67. Simons M, Kee EG, Kimble R, Tyack Z. Ultrasound is a reproducible and valid
tool for measuring scar height in children with burn scars: a cross-sectional
study of the psychometric properties and utility of the ultrasound and 3D
camera. Burns. 2017;43(5):993–1001.
68. Draaijers LJ, Tempelman FR, Botman YA, Kreis RW, Middelkoop E, van
Zuijlen PP. Colour evaluation in scars: tristimulus colorimeter, narrow-band
simple reflectance meter or subjective evaluation? Burns. 2004;30(2):103–7.
69. Stevens KJ. Working with children to develop dimensions for a preference-
based, generic, pediatric health-related quality-of-life measure. Qual Health
Res. 2010;20:340–51.
70. Stevens KJ. Developing a descriptive system for a new preference-based
measure of health-related quality of life for children. Qual Life Res. 2009;
18(8):1105–13.
71. Stevens KJ. Assessing the performance of a new generic measure of health
related quality of life for children and refining it for use in health state
valuation. Appl Health Econ Health Policy. 2011;9(3):157–69.
72. Stevens K. The Child Health Utility 9D (CHU9D) – A New Paediatric Preference
Based Measure of Health Related Quality of Life. PRO Newsletter. 2010;43:11.
73. Revicki DA. Patient assessment of treatment satisfaction: methods and
practical issues. Gut. 2004;53(suppl 4):iv40.
74. Willebrand M, Sjöberg F, Huss F, Sveen J. Parents’ perceived quality of
pediatric burn care. J Crit Care. 2018;43:256–9.
75. Lakatos E. Sample Sizes Based on the Log-Rank Statistic in Complex Clinical
Trials. Biometrics. 1988;44:229–41.
76. Lakatos E. Designing Complex Group Sequential Survival Trials. Stat Med.
2002;21:1969–89.
77. Snow G. blockrand: Randomization for block random clinical trials
2013: Available from: https://CRAN.R-project.org/package=blockrand.
[cited 2018. 1.3]
78. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research
electronic data capture (REDCap) – a metadata-driven methodology and
workflow process for providing translational research informatics support.
J Biomed Inform. 2009;42(2):377–81.
79. Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krleza-Jeric K,
et al. SPIRIT 2013 statement: defining standard protocol items for clinical
trials. Ann Intern Med. 2013;158(3):200–7.
80. Chan AW, Tetzlaff JM, Gotzsche PC, Altman DG, Mann H, Berlin JA, et al.
SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical
trials. BMJ. 2013;346:e7586.
81. Brown NJ, Kimble RM, Gramotnev G, Rodger S, Cuttle L. Predictors of
re-epithelialization in pediatric burn. Burns. 2014;40(4):751–8.
82. McGarry S, Burrows S, Ashoorian T, Pallathil T, Ong K, Edgar DW, et al.
Mental health and itch in burns patients: potential associations. Burns.
2016;42(4):763–8.
83. Moher D, Hopewell S, Schulz KF, Montori V, Gøtzsche PC, Devereaux PJ, et al.
CONSORT 2010 explanation and elaboration: updated guidelines for reporting
parallel group randomised trials. J Clin Epidemiol. 2010;63(8):e1–e37.